A unique live attenuated simian immunodeficiency virus that encodes the capability to excise its integrated proviral genome from the infected cell's genome after limited rounds of virus replication was generated. This attenuated virus strain contains four specific mutations in its proviral genome. First, the 3' long terminal repeat (LTR) contains an engineered IoxP site. Second, the ATG codons of nef gene that overlap with gp41 was mutated to abolish the translation start codons. Third, the non-overlapping region of nef between gp41 and the 3' LTR was excised and replaced with a minimal DNA segment containing a unique Mlu1 restriction endonuclease site. Lastly, DNA encoding the bacteriophage P1 cre recombinase gene was cloned into the unique Mlu1 site within the proviral genome. Since this gene is flanked by unique Mlu1 restriction endonuclease sites, the cre recombinase gene was positioned in either the sense or antisense orientation. Live attenuated viruses such as these have not been generated or proposed by others in the field of acquired immunodeficiency syndrome (AIDS) research. Extensive evaluation of unique live attenuated vaccines of SIV in rhesus macaques may provide the means for creating a safe, effective, live attenuated vaccine to protect against AIDS.